Paraquat causes an increase in the biosynthesis of the manganese superoxide dismutase in E. coli. This a secondary consequence of an increased intracellular production of 02 anion in the presence of paraquat. We will now test whether paraquat similarly causes induction of superoxide dismutase in mammalian cells and whether the increased production of 02 anion, in its presence, is a component of its toxicity. Manipulation of the intracellular level of superoxide dismutase with paraquat will also be useful in studies of the biological significance of this enzymic activity. Mutants of E. coli have been prepared with specific defects in the iron and in the manganese superoxide dismutases. These mutants will be compared with the parental strain in order to elucidate the biological functions of these enzymes and to expose the consequences of deficiencies of these activities. The diminution of the oxygen enhancement of radiation lethality by superoxide dismutase will be further studied in order to explore the mechanism of this effect.